Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes

✍ Scribed by Koji Kono; Yang Rongcun; Jehad Charo; Fumiko Ichihara; Esteban Celis; Alessandro Sette; Ettore Appella; Takayoshi Sekikawa; Yoshiro Matsumoto; Rolf Kiessling

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: French
• Weight: 127 KB
• Volume: 78
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19981005)78:2<202::aid-ijc14>3.0.co;2-c

✦ Synopsis

We have derived HLA-A2.1-restricted, gastric cancerspecific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor-associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1 ؉ , HER2/neu ؉ gastric cancer cells, HER2/ neu-transfected C1R/A2 cell lines (HLA-A2.1 ؉ , HER2 ؉ ) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1 ؉ , HER2 ؉ ). This recognition could be inhibited by anti-HLA-A2 antibody or by cold target HER2/neu-transfected C1R/A2 cells. Our results demonstrate that the HER2/neu-encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines. Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9 106 ), HER2(9 369 ), HER2(9 689 )], which all bound HLA-A2.1 with high (IC 50 F 50 nM) affinity, were able to sensitize HLA-A2 ؉ C1R/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes. In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric cancer.